Methods of treatment with a fusion protein comprising IL-4 and IL-10

Abstract

The invention is concerned with a fusion protein comprising interleukin 10 and interleukin 4, a nucleic acid molecule encoding such fusion protein, a vector comprising such nucleic acid molecule, and a host cell comprising such nucleic acid molecule or such vector. The invention further pertains to a method for producing such fusion protein. The fusion protein or a gene therapy vector encoding the fusion protein may be used in the prevention or treatment of osteoarthritis, chronic pain, a condition characterized by local or systemic inflammation, immune activation, and/or lymphoproliferation.

The invention claimed is: 
     
       1. A method of treating chronic pain, local inflammation, or systemic inflammation, comprising administering to a human patient in need thereof an effective amount of a pharmaceutical composition that comprises:(a) a fusion protein consisting of, from N- to C-terminal, a human IL-4, a linker, and a human IL-10; or from N- to C-terminal, a human IL-10, a linker, and a human IL-4; and (b) a pharmaceutically-acceptable excipient, carrier, or diluent;
 wherein the human IL-4 consists of an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 1, the linker consists of the amino acid sequence of SEQ ID NO: 3, and the human IL-10 consists of an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 2; and wherein the effective amount is 0.5 μg to 1 mg per kg of body weight of the patient. 
 
     
     
       2. The method of  claim 1 , wherein the pharmaceutical composition that comprises the fusion protein is administered in one or more unit dosage forms. 
     
     
       3. The method of  claim 1 , wherein the pharmaceutical composition that comprises the fusion protein is administered in multiple doses. 
     
     
       4. The method of  claim 1 , wherein the pharmaceutical composition is a controlled release formulation. 
     
     
       5. The method of  claim 1 , wherein the pharmaceutical composition that comprises the fusion protein is administered parenterally. 
     
     
       6. The method of  claim 1 , wherein the pharmaceutical composition that comprises the fusion protein is administered systemically. 
     
     
       7. The method of  claim 1 , wherein the pharmaceutical composition that comprises the fusion protein is administered intrathecally. 
     
     
       8. The method of  claim 1 , wherein the pharmaceutical composition that comprises the fusion protein is administered by intra-articular injection. 
     
     
       9. The method of  claim 1 , wherein the pharmaceutical composition that comprises the fusion protein is administered by infusion. 
     
     
       10. The method of  claim 1 , wherein the fusion protein consists of, from N- to C-terminal, the human IL-4, the linker, and the human IL-10. 
     
     
       11. The method of  claim 1 , wherein the fusion protein consists of, from N- to C-terminal, the human IL-10, the linker, and the human IL-4. 
     
     
       12. The method of  claim 1 , wherein administering the pharmaceutical composition that comprises the fusion protein reduces the chronic pain, the local inflammation, or the systemic inflammation to a greater extent than administering the human IL-4, the human IL-10, or a combination thereof. 
     
     
       13. The method of  claim 1 , wherein administering the pharmaceutical composition that comprises the fusion protein reduces the chronic pain, the local inflammation, or the systemic inflammation for a longer period of time than administering the human IL-4, the human IL-10, or a combination thereof. 
     
     
       14. The method of  claim 1 , wherein the chronic pain is neuropathic pain. 
     
     
       15. The method of  claim 1 , wherein the chronic pain is inflammatory pain. 
     
     
       16. The method of  claim 1 , wherein the chronic pain, the local inflammation, or the systemic inflammation is associated with one or more of: osteoarthritis, sepsis, adult respiratory distress syndrome, allotransplantation, xenotransplantation, dermatitis, inflammatory bowel disease, sarcoidosis, allergies, psoriasis, ankylosing spondylarthritis, autoimmune diseases, glomerulonephritis, immune complex-induced and other forms of vasculitis, multiple sclerosis, Sjogren's disease, gout, burn injuries, multiple trauma, stroke, myocardial infarction, atherosclerosis, diabetes mellitus, extracorporeal dialysis and blood oxygenation, ischemia-reperfusion injuries, toxicity induced by the in vivo administration of cytokines or therapeutic monoclonal antibodies, chronic pain syndrome and neuropathic and/or inflammatory pain. 
     
     
       17. The method of  claim 1 , wherein the chronic pain, the local inflammation, or the systemic inflammation is associated with osteoarthritis. 
     
     
       18. A method of treating chronic pain, local inflammation, or systemic inflammation, comprising administering to a human patient in need thereof an effective amount of a fusion protein that comprises IL-4 and IL-10, wherein the fusion protein comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 4; and wherein the IL-4 and the IL-10 are linked by a linker consisting of the amino acid sequence of SEQ ID NO: 3. 
     
     
       19. The method of  claim 18 , wherein the fusion protein further comprises one or more chemical modifications. 
     
     
       20. The method of  claim 19 , wherein the chemical modification is selected from the group consisting of glycosylation, fucosylation, sialylation, and pegylation. 
     
     
       21. The method of  claim 18 , wherein the fusion protein comprises the amino acid sequence of SEQ ID NO: 4. 
     
     
       22. The method of  claim 18 , wherein the fusion protein consists of the amino acid sequence of SEQ ID NO: 4.